DESCRIPTION (provided by candidate): This is a request for five more years of support via a NIH Independent Scientist Award (K02). I have long sought to integrate psychosocial and biological models of depression. I want to enhance my understanding of neurobiology and developmental processes in the nature and treatment of depression and to gain a better sense of basic genetic factors. I also want to continue to enhance the clinical realism (effectiveness) of my work. I am interested in whether cognitive therapy (CT) has a more enduring effect than antidepressant medications (ADM) and whether that enduring effect can extend to the prevention of depression in at-risk adolescents. We recently completed a placebo-controlled trial that showed that CT is as efficacious as ADM in the treatment moderate to severe depression and good as continuation ADM and better than ADM withdrawal in the prevention of subsequent relapse following treatment termination. I also completed a trial with colleagues in Seattle that largely replicated these findings and further suggested that behavioral activation (BA) may be superior to CT in the treatment of more complex patients. We are conducting a multisite trial with colleagues at Penn and Rush that asks whether adding CT to ADM can eliminate the need to keep patients on maintenance medications. We continue to study the impact of treatment on the offspring of our depressed patients and we plan to examine the genetic factors that moderate and the neurobiological processes that mediate CT's enduring effect. Finally, we are conducting a study to see if CBT can be used to prevent the onset of depression in at-risk adolescents and also plan to implement a placebo-controlled comparison of BA and ADM (alone and in combination) in the treatment of adolescent depression with colleagues in Seattle. My goal throughout has been to examine the role of both psychological and biological processes in the moderation and mediation of treatment effects and to do so in a manner that has the greatest possible impact on actual clinical practice.